Proteomics

Dataset Information

0

The polyamine-hypusine circuit controls an oncogenic translational program necessary for MYC-driven lymphomagenesis


ABSTRACT: MYC oncogenes are activated in broad spectrum of human malignancies and transcriptionally reprogram the genome to drive cancer cell growth. Given this it is unclear if targeting a single effector will have a therapeutic benefit. MYC activates the polyaminehypusine circuit, which post-translationally modifies the translation factor eIF5A. The hypusine axis has been proposed to suppress tumorigenesis. Here we report essential roles for hypusinated eIF5A in the development and maintenance of Myc-driven lymphoma, where loss of eIF5A hypusination abolishes malignant transformation. Mechanistically, integrating RNA-seq, Ribo-seq and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including key regulators of G1 to S phase cell cycle progression. Notably, this circuit controls Myc’s proliferative response at several levels, and it is activated across multiple tumor types. These findings suggest the hypusine circuit as a therapeutic target for a broad spectrum of malignancies.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, B Cell

DISEASE(S): Burkitt Lymphoma

SUBMITTER: John Koomen  

LAB HEAD: John Cleveland

PROVIDER: PXD031361 | Pride | 2024-01-26

REPOSITORIES: Pride

altmetric image

Publications

The Polyamine-Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma.

Nakanishi Shima S   Li Jiannong J   Berglund Anders E AE   Kim Youngchul Y   Zhang Yonghong Y   Zhang Ling L   Yang Chunying C   Song Jinming J   Mirmira Raghavendra G RG   Cleveland John L JL  

Blood cancer discovery 20230701 4


The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine-hypusine circuit, which posttranslationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and  ...[more]

Similar Datasets

2016-07-09 | PXD000880 | Pride
2022-11-11 | PXD021063 | Pride
2023-05-10 | PXD040460 | Pride
2008-06-13 | E-GEOD-5290 | biostudies-arrayexpress
2022-06-24 | GSE192566 | GEO
2006-07-12 | GSE5290 | GEO
2019-08-30 | GSE136581 | GEO
2021-09-08 | PXD015414 | Pride
2020-02-17 | PXD015424 | Pride
2024-10-27 | GSE279773 | GEO